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Objectives: In view of the neuroprotective characteristic of cannabidiol (CBD) and its beneficial action on aversive memory in non-diabetic animals, we aimed to investigate in animals with experimentally induced type-1 diabetes mellitus (T1DM) whether CBD treatment would be able to impair the contextual fear memory consolidation, its generalisation and whether the effect would be lasting. We also investigated the CBD effect on anxiety-like responses. Methods: After T1DM induction, animals received single or more prolonged treatment with CBD and were submitted to the contextual fear conditioning test. As expression of activity-regulated cytoskeletal-associated (Arc) protein is necessary for memory consolidation, we evaluated its expression in the dorsal hippocampus (DH). For evaluating anxiety-related responses, animals were submitted to the elevated plus maze test (EPMT), in which the time and number of entries in the open arms were used as anxiety index. Results: A single injection of CBD impaired the contextual fear memory consolidation and its generalisation, which was evaluated by exposing the animal in a neutral context. This single injection was able to reduce the elevated expression of Arc in the DH from these animals. Interestingly, more prolonged treatment with CBD also impaired the persistence of context-conditioned fear memory and induced an anxiolytic-like effect, as the treated group spent more time in the open arms of the EPMT. Conclusion: CBD interferes with contextual fear memory and the dosage regimen of treatment seems to be important. Moreover, we cannot rule out the involvement of emotional aspects in these processes related to fear memory.

Background.What determines inter-individual variability to impairments in behavioural control that may underlie road-traffic accidents, and impulsive and violent behaviours occurring under the influence of cannabis, the most widely used illicit drug worldwide?Method.Employing a double-blind, repeated-measures design, we investigated the genetic and neural basis of variable sensitivity to cannabis-induced behavioural dyscontrol in healthy occasional cannabis users. Acute oral challenge with placebo or Δ9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, was combined with functional magnetic resonance imaging, while participants performed a response inhibition task that involved inhibiting a pre-potent motor response. They were genotyped for rs1130233 single nucleotide polymorphisms (SNPs) of the protein kinase B (AKT1) gene.Results.Errors of inhibition were significantly (p = 0.008) increased following administration of THC in carriers of the A allele, but not in G allele homozygotes of theAKT1rs1130233 SNP. The A allele carriers also displayed attenuation of left inferior frontal response with THC evident in the sample as a whole, while there was a modest enhancement of inferior frontal activation in the G homozygotes. There was a direct relationship (r = − 0.327,p = 0.045) between the behavioural effect of THC and its physiological effect in the inferior frontal gyrus, whereAKT1genotype modulated the effect of THC.Conclusions.These results require independent replication and show that differing vulnerability to acute psychomotor impairments induced by cannabis depends on variation in a gene that influences dopamine function, and is mediated through modulation of the effect of cannabis on the inferior frontal cortex, that is rich in dopaminergic innervation and critical for psychomotor control.

Background:Depression is the most common psychiatric manifestation in patients with Parkinson's disease (PD). In addition, depressive symptoms may be considered to be a prodromal manifestation of PD. In recent years, the association between PD and depression has been the focus of neuroimaging studies using functional and structural techniques.Methods:The aim of this study was to review the main neuroimaging studies assessing the comorbidity between depression and PD. Literature searches were conducted to find the major neuroimaging studies that consider primarily the comorbidity between depression and PD using the indices Web of Science and Lilacs.Results:In total, 296 papers were identified, and 18 of these studies were selected for the current review. The principal neuroimaging technique used was SPECT. The structural neuroimaging studies that have evaluated the impact of current or previous bouts of depression on the neurodegenerative process of PD are scarce and inclusive. The instruments that were used to evaluate depression differed among the studies. Several brain regions appear to be involved in depression, particularly the limbic system and the basal ganglia. In addition, the serotonergic, dopaminergic, and noradrenergic systems also appear to be associated with depressive symptoms in PD.Conclusion:Several brain regions and neurotransmitter systems are involved in depression in PD; however, the variety of criteria used to evaluate depressive symptoms precludes more specific conclusions.

Réus GZ, Stringari RB, Ribeiro KF, Luft T, Abelaira HM, Fries GR, Aguiar BW, Kapczinski F, Hallak JE, Zuardi AW, Crippa JA, Quevedo J. Administration of cannabidiol and imipramine induces antidepressant-like effects in the forced swimming test and increases brain-derived neurotrophic factor levels in the rat amygdala.Objective:Cannabidiol is a chemical constituent fromCannabis sativaand it has multiple mechanisms of action, including antidepressant effects. The main objective of the present study was to evaluate behavioural and molecular effects induced by administration of cannabidiol and imipramine in rats.Methods:In the present study, rats were acutely or chronically treated for 14 days once a day with saline, cannabidiol (15, 30 and 60 mg/kg) or imipramine (30 mg/kg) and the animals behaviour was assessed in forced swimming and open-field tests. Afterwards, the prefrontal cortex, hippocampus and amygdala brain-derived neurotrophic factor (BDNF) levels were assessed by enzyme-linked immunosorbent sandwich assay.Results:We observed that both acute and chronic treatments with imipramine at the dose of 30 mg/kg and cannabidiol at the dose of 30 mg/kg reduced immobility time and increased swimming time; climbing time was increased only with imipramine at the dose of 30 mg/kg, without affecting locomotor activity. In addition, chronic treatment with cannabidiol at the dose of 15 mg/kg and imipramine at the dose of 30 mg/kg increased BDNF levels in the rat amygdala.Conclusion:In conclusion, our results indicate that cannabidiol has an antidepressant-like profile and could be a new pharmacological target for the treatment of major depression.

PurposeTo perform a psychometric analysis of the Brazilian version of the Brief Social Phobia Scale (BSPS).Materials and methodsHundred and seventy-eight university students of both genders aged on average 21.2 years and identified as Social Anxiety Disorder (SAD) cases and non-cases was studied, with the structured clinical interview for DSM-IV being used as a parameter. The different instruments were applied in an individual manner in the presence of a rater and of an observer.ResultsThe BSPS showed adequate internal consistency (0.48–0.88) and concurrent and divergent validity with the Beck Anxiety Inventory (BAI) (0.21–0.62), Social Phobia Inventory (0.24–0.82) and Self Statements During Public Speaking Scale (SSPS) (0.23–0.31). Discriminative validity revealed a sensitivity of 0.88–0.90 and a specificity of 0.81(0.83 for cut-off notes of 18/19. Factorial analysis demonstrated the presence of six factors that jointly explained 71.79% of data variance. Construct validity indicated some limits of the scale regarding the diagnosis of SAD. Inter-rater reliability was strong (0.86–1.00, p < 0.001).ConclusionsThe BSPS is adequate for use with university students, although further studies in different cultures, samples and contexts are still necessary.

ObjectiveThis study aimed to evaluate the discriminative validity of MINI-SPIN (MS) as a screening tool for social anxiety disorder (SAD) in a group of Brazilian university students.MethodSPIN was collectively applied to 2320 university students. Among them, 656 individuals who fulfilled the criteria for positive MS (N = 473) and negative MS (N = 183) were selected and divided into two groups. The selected subjects were interviewed by telephone using the SAD module of the SCID-IV, used as the gold standard. In order to check interrater reliability, a group of university students (N = 57) was reinterviewed by telephone by a second rater, and another group (N = 100) participated in a face-to-face interview.ResultsThe Kappa coefficient among the telephone interviews was 0.80, and a coefficient of 0.84 (P < 0.001) was obtained between the telephone interview and the face-to-face one. For a cut-off score of 6, suggested in the original English version of the instrument, sensitivity was 0.94, specificity 0.46, the positive predictive value (PPV) was 0.58, and the negative predictive value (NPV) was 0.92. For a cut-off score of 7, we observed an increase in the specificity and in the PPV (0.68 and 0.65) while the sensitivity and NPV (0.78 and 0.80) remained high.Discussion/ConclusionMS showed quite satisfactory psychometric qualities. The cut-off score of 6 seemed to be the most suitable to attest the tracking value of the tool. However, the cut-off score of 7 was the most suitable as a minimum parameter for the studied group, with psychometric values more similar to those of the original study.

IntroductionMusic performance anxiety (MPA) is a persistent and distressing experience that involves apprehension linked with musical performance in public (individual or collective). Anxious individuals concentrate their anxiety in situations that involve social scrutiny, favoring distorted, dysfunctional, and negative interpretations of that situation followed by experiences of physiological symptoms associated with the exposure. The most commonly used substances in the pharmacological management of MPA are beta-blockers and benzodiazepines. However, these options are not fully efficient and cause relevant side effects that interfere mainly with performance. Therefore, investigations on alternative substances to treat MPA are highly opportune.ObjectiveTo assess the acute effects of oxytocin (OT) on physiological and cognitive variables during an experimental model of simulated performance.MethodsWe assessed 12 musicians with MPA pre-treated with intranasal OT (24 UI) or placebo in a crossover trial involving an experimental situation of public performance. Cognitive and physiological measures (heart rate, blood pressure, salivary cortisol) were recorded before/during performance (anticipatory performance anxiety). Statistical analyses were made using Stata Direct.ResultsThe results showed no effects of OT on physiological symptoms (P > 0.190). In respect to anticipatory anxiety, however, we found a tendency for OT to reduce negative cognitions associated with music performance (P = 0.06). No side effects were reported by musicians throughout the trial.ConclusionThese tendencies, if confirmed through the expansion of the sample, have important implications for the practice of amateur and professional musicians who could benefit from interventions as the one described, possibly with a lesser impact of side effects.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Introduction Anxiety may be associated with diverse medical conditions, among which joint hypermobility syndrome. Joint hypermobility (JHM) is characterized by increased elasticity and can be advantageous in specific activities, such as dance or gymnastics. On the other hand, joint hypermobility syndrome (JHS) is a more complex condition including other clinical symptoms, especially a history of injuries, skin signs, instability and pain. Objectives To investigate the prevalence of JHM and JHS throughout ballet career and the association between anxiety and joint hypermobility in a sample consisting of ballet dancers. Methods study included 145 dancers, divided into three groups: students (n=59), teachers (n=37) and professional ballerinas (n=49). Participants completed self-rating instruments assessing JHM (five-part questionnaire), anxiety (BAI), social anxiety (SPIN), panic (Patient Health Questionnaire – Brief PHQ) and pain (Brief Pain Inventory [BPI]; Self-Estimated Functional Inability because of Pain [SEFIP]). Ballet dancers also underwent a clinical evaluation based on Beighton score and Brighton criteria. Results Participants with JHM had higher scores in neurophysiological subscale of the BAI, but less social anxiety symptomatology. JHS correlated with the subjective and panic subscales of the BAI and with SPIN. Participants with JHS also presented higher scores in specific items of BAI as in specific items of SPIN. Conclusions our data suggest that JHS seems to be more consistently associated with anxiety than the 'isolated hypermobility” (JHM). Nevertheless, the strenght of the correlation between anxiety and JHS was moderate. Data also provided elements to discuss important features of JHM, JHS and pain throughout the ballet career.

Introduction The growing concern about cannabis use, the most used illicit drug worldwide, has led to an increase in the number of cannabis studies using neuroimaging techniques to determine its effect on brain structure and function. Aims We conducted a systematic review to assess the evidence of the impact of chronic cannabis use on brain structure and function in adults and adolescents. Methods Papers published until August 2012 were included from EMBASE, Medline, PubMed and LILACS databases following a comprehensive search strategy and pre-determined set of criteria for article selection. Only neuroimaging studies involving chronic cannabis users with a matched control group were considered. Results One hundred and forty-two studies were identified, of which 43 met the established criteria. Eight studies were in adolescent population. Neuroimaging studies provide evidence of morphological brain alterations in both population groups, particularly in the medial temporal and frontal cortices, as well as the cerebellum. These effects may be related to the amount of cannabis exposure. Functional neuroimaging studies suggest different patterns of resting global and brain activity during the performance of several cognitive tasks also in both groups, which may indicate compensatory effects in response to chronic cannabis exposure. The results pointed out methodological limitations among studies and high heterogeneity in the findings. Conclusion Chronic cannabis use may alter brain structure and function in adult and adolescent population. Further studies should consider the use of convergent and multimodal methodology, prospective large samples involving adolescent to adulthood subjects, and data-sharing initiatives. Grants: PNSD/2011/050, PNSD2006/101, SGR2009/1435.

Background There is increasing data supporting the role of endocannabinoid system (eCB) in the control of emotional homeostasis, mainly acting through CB1R activation (MenchoulamP Marco et al., 2012). The cannabinoid receptor 1 (CNR1) gene has been associated to “high neuroticism” and “low agreeableness” phenotype (Juhasz et al., 2009). Aims Study the association between personality traits and genetic polymorphisms located in genes related to eCB ( CNR1, CNR2, FAAH and MGKLL ) in patients with anxiety disorders. Methods In a case-control study, we analyzed 48 polymophisms tagSNPs in sample of 507 Caucasians subjects of both genders. All were assessed using the Semi-Structural Interview of DSM-IV criteria and the Temperament and Character Inventory of Cloninger. Multiple regression analysis was used to determine whether the different personality traits were associated with each variant in CNr1, CNr2, FAAH, and MGKLL , using age and gender as confounder variables. Results A significant association was found between “high Harm-avoidance” trait and rs1049353 in the CNR1 gene (p FAAH gene (p FAAH gene (p Conclusions These findings suggest that genetic variations in the CNR1 and FAAH genes may modulate the expression of some clinical aspects of anxiety traits and probably anxiety disorders. Grants: ICIII G03/184; SGR2009/1435 .

BackgroundAlthough there is considerable evidence on the impact of negative life events during childhood on the etiology of psychiatric disorders, little is known about the specific influence on the social anxiety disorder. The objective of the study was to examine this association.MethodIn a cross-sectional survey in 571 university students we analysed the association between loss of someone close, emotional abuse, physical abuse, family violence and sexual abuse with social anxiety assessed by the Liebowitz Social Anxiety Scale.ResultsTwenty percent of the sample had social anxiety and 50,6% had an early negative life events in childhood. After controlling for family psychiatric history and gender only family violence was associated with an increased risk of social anxiety (OR = 4.63; 95%CI = 1.13–18.9).ConclusionsThis study found childhood family violence associated with social phobia in university students.

ObjectiveThe diagnostic boundaries of social anxiety disorder (SAD) are still controversial and recent evidence suggests that the condition could be better understood as a continuum of severity, rather than a strictly circumscribed entity. Current neuroanatomical theories on SAD support the involvement of limbic structures in its pathophysiology, with an emphasis on the amygdala. Thus, the objective of this study was to investigate the hypothesis of volumetric alterations in the amygdala of subjects in different points of the social anxiety spectrum.MethodThe sample consisted of patients with generalized SAD (n=17), subthreshold SAD (increased social anxiety without avoidance; n=13), and healthy controls (n=15). Participants underwent structural magnetic resonance scans and the volume of the bilateral amygdala was manually determined.ResultsSignificantly greater volumes of bilateral amygdala were found in socially anxious individuals. Amygdala volumes of subthreshold SAD participants fell between the values found for generalized SAD and healthy controls.ConclusionsIndividuals suffering from SAD have greater amygdala volumes compared to controls and this difference seems to be in agreement with the theoretical conception of SAD as a severity continuum and not as a circumscribed nosological entity.

IntroductionDepersonalization (DP) is a common and complex clinical phenomenon in neurology and psychiatry. It is defined as an experience in which the individual feels a sense of unreality and detachment from him/herself. Prevalence and clinical correlates of dissociative symptoms in general, and DP in particular have been associated to panic disorder (Hunter et al., 2004). Moreover, DP has been associated with certain personality traits, specifically “harm-avoidant” temperament dimension, immature defenses, and overconnection and disconnection cognitive schemata (Simeon et al., 2002).ObjectivesTo investigate the prevalence of DP syndrome in panic disorder and its relationship with personality.MethodsOne-hundred-four consecutive adult patients with panic disorder were assessed with the Semi- Structured Clinical Interview for DSM-IV-Axis I and II. All participants were evaluated with the Cambridge Depersonalization Scale (Sierra and Berrios, 2000) and the Cloninger Temperament and Character Inventory. The severity of panic disorder was measured with the Panic and Agoraphobia Scale.ResultsSeventeen patients (16.3%) had a DP syndrome. There were not socio-demographic differences between both groups with and without DP syndrome. Patients with DP syndrome showed a higher score in “self-transcendence” character dimension (p< .001), higher prevalence of personality disorders (p=.007) and greater severity of panic disorder (p=.007). A logistic regression analysis showed that severity of panic disorder (p=.031) and higher “self-transcendence” personality dimension (p=.019) predicts DP syndrome in panic disorder patients. The Hosmer-Lemeshow test showed the goodness-of-fit of the model.ConclusionsThe study confirms the association of DP syndrome with panic disorder and their relationship with “self-transcendence” personality dimension.

Background:This study examined the effect of Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on brain activation during a motor inhibition task.Methods:Functional magnetic resonance imaging and behavioural measures were recorded while 15 healthy volunteers performed a Go/No-Go task following administration of either THC or CBD or placebo in a double-blind, pseudo-randomized, placebo-controlled repeated measures within-subject design.Results:Relative to placebo, THC attenuated activation in the right inferior frontal and the anterior cingulate gyrus. In contrast, CBD deactivated the left temporal cortex and insula. These effects were not related to changes in anxiety, intoxication, sedation, and psychotic symptoms.Conclusions:These data suggest that THC attenuates the engagement of brain regions that mediate response inhibition. CBD modulated function in regions not usually implicated in response inhibition.

The prevalence of social anxiety is estimated of 7-12% of the general population and 18% of university student. Social anxiety has a high prevalence of psychiatry and personality comorbidity. At age of 18-25 years old 80% of social anxiety cases have onset. To detect social anxiety at that age maybe important to avoid chronicity of the illness.Aims:To study personality traits associated with social anxiety in university students.Methods:We designed a cross-sectional study at the Autonomous University of Barcelona. Student were recruited by an advertisement. All student signed the informed consent. We collected: Socio-demographic data, personal and family psychiatry history, and the Liebowitz Anxiety Scale (LSAS) and the Temperament and Character Inventory of Cloninger. We defined as a social anxiety group a LSAS ≥50 total score.Results:Five hundred ninety-one students enter in the study. Final sample after excluded those who did not filled the rating scales was 574 participants: 75% were women, mean age (SD): 22.7 (5.3), 156 (124 women/32 men), 26% had social anxiety. Eighteen percent had family and 22% personal psychiatry history. The personality profile of the social anxiety group was: high harm avoidance (HA) (p< .001), low novelty seeking (NS) (p< .001), and low self-directedness (SD) (p< .001).By logistic regression, after corrected by sex, age, personal and family psychiatry history, HA (OR=1.118; 95%CI=1.081-1.155), NS (OR=0.954;95%CI=0.927-0.982) and SD (OR=0.957;95%CI=0.930-0.985) predicted social anxiety. R2Nagelkerke=0.442. Hosmer-Lemeshow test (p>.05).Conclusions:A profile of high HA, low NS and SD personality dimensions may predict those university students with social anxiety.

Background and Aims:Panic disorder (PD) is a common and debilitating anxiety disorder. Recent neuroanatomical theories of PD propose an extensive involvement of limbic system in pathophysiology of this condition. In fact, several structural and functional neuroimaging studies have shown changes in limbic structures, such as hippocampus in PD patients. Despite this, no prior studies have examined hippocampal neurochemistry in this disorder. The current study used proton magnetic resonance spectroscopy imaging (1H-MRSI) to examine possible neurochemical abnormalities in hippocampus in PD patients.Methods:Twenty-five patients meeting the DSM-IV criteria for PD and eighteen psychiatrically healthy controls were investigated. The subjects were paired based on gender, age, years of education, handedness, and socioeconomic level. N-acetylaspartate (NAA, a putative marker of neuronal viability) and choline (Cho, involved in the synthesis and degradation of cell membranes) levels were quantified relative to creatine (Cr, which is thought to be relatively stable among individuals and in most brain areas) in both right and left hippocampus.Results:Compared with controls, panic patients demonstrated significantly lower NAA/Cr in the left hippocampus. No other difference was detected.Conclusions:This result is consistent with the previous findings of hippocampal alterations in PD and provides the first neurochemical suggesting of involvement of this structure in the disorder.